Methyl morpholine oxide → 6-(4-fluorobenzoyl)-5,6,7,8-tetrahydro-4H-oxazolo[4,5-d]azepine-2-methanol

Temperature

100 °C

A 2.5% solution of osmium tetraoxide in tert-BuOH (0.064 mL, 0.005 mmol) was added to a stirred solution of 6-(4-fluorobenzoyl)-5,6,7,8-tetrahydro-2-[(E)-2-phenylethenyl]-4H-oxazolo[4,5-d]azepine (0.037 g, 0.10 mmol) and N-methylmorpholine-N-oxide (0.024 g, 0.20 mmol) in a mixture of THF (0.5 mL) and H2O (0.10 mL). The mixture was stirred at 100° C. for 5 minutes under microwave irradiation. The solvent was evaporated in vacuo and the crude product dissolved in a mixture of MeOH (0.5 mL) and THF (0.5 mL). Then sodium periodate (0.087 g, 0.41 mmol) was added and the mixture stirred at 120° C. for 15 minutes. The mixture was cooled down to 0° C. and sodium borohydride (0.0.15 g, 0.41 mmol) was added portionwise. The mixture was stirred at room temperature for 15 minutes, diluted with a saturated solution of NH4Cl and extracted with AcOEt. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo to yield 6-(4-fluorobenzoyl)-5,6,7,8-tetrahydro-4H-oxazolo[4,5-d]azepine-2-methanol (0.02 g, 67% yield) as a yellow oil that was used in the next step without further purification. C15H15FN2O3 LCMS: Rt 1.74, m/z 291 [M+H]+ (using method, LC-MS Method 2).

1. customThe solvent was evaporated in vacuo
2. dissolutionthe crude product dissolved in a mixture of MeOH (0.5 mL) and THF (0.5 mL)
3. stirringthe mixture stirred at 120° C. for 15 minutes
4. temperatureThe mixture was cooled down to 0° C.
5. stirringThe mixture was stirred at room temperature for 15 minutes
6. extractionextracted with AcOEt
7. customThe organic layer was separated
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customthe solvents evaporated in vacuo

ORD record

ord-f8710b912cfb45d79cb1ae54b4be317d

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09090632B2